Zinc salts of mono-olefinic acids as antimycotics



Patented June 13, 1950 ZINC SALTS F MONO-OLIFINIO ACIDS AS ANTIMYCOTICS John 0. Baker, Hewitt, N. 1., assignor to Wallace & Tiernan Products, Inc., corporation of New Jersey Belleville, N. L, 8

No Drawing. Application In]! I, 1949, Serial N0. 103,522

The present invention relates to an antimycotic composition useful in the treatment 01' superficial fungus infection of humans and higher animals. This application is a continuation-in-part of my copending application Serial No. 589,698, filed April 21, 1945 for Antimycotic composition.

A great deal of research work has been done in the past looking toward, the preparation of suitable therapeutic antimycoticy ihpositions for the treatment of this type on iirecticn, which is very common among large numbersof people, and is also at times a serious detriment to the personnel in our armed forces.

In the past, various materials have been suggested and many actually used for the treatment of this type of infection, including, for example, boric acid, salicylic acid, and sulfur (powder). It has been suggested to use both saturated and unsaturated fatty acids with various numbers of carbon atoms. Zinc salts have also been independently suggested for use: see Patent No. 2,190,714, wherein salts of saturated acids from 3 to 12 carbon atoms are disclosed and wherein zinc salts are also disclosed. Proponic acid has also been mentioned as a fungistatic agent. In view of the fact that this infection is quite diflicult to control and as certain cases respond better to some treatments than to others; and conversely, as various of those materials above referred to have better effects on some persons than on others, there is still a substantial need in the treatment of this type of infection for additional and more eifective materials, or combinations thereof in the treatment of many cases of infections of this type. In general, the results obtained by previously available materials are often unsatisfactory and seldom completely satisfactory.

Among the objects of the present invention, therefore, are to provide a more satisfactory therapeutic composition for the treatment of fungus infections of the type referred to, which will give superior results as contrasted with previously available materials and in some instances which will give positively desirable results in cases where the previously available materials would not give satisfactory results. i

A more specific object of this invention is to provide an antimycotic preparation, which is compatible with the normal function of the skin, which produces no irritating effects upon the skin, even when used in large quantities; and yet which produces a. powerful antimycotic action.

A further detailed object of the present invention is to provide a preparation or composition, which contains an eifective antimycotic agent in sparingly soluble form from which it may be slowly liberated.

A further object of the present invention is to provide an antimycotic agent, which, at the same time, is a good drying agent. 1

Another object of the present invention is to provide an antimycotic agent having physical properties which make it suitable foruse as a dermatologic dusting powder and which also may I be prepared in the form of an ointment without the addition of another solid phase.

One of the well recognized problems in therapeutics is to. provide a therapeutic agent in such form that a high concentration of the agent is never present in or on the body and yet which provides an even or stationary release of the active agent. This is 01' particular importance in the case of agents applied to the skin as this orgen is very sensitive. It responds to irritating stimuli with an inflammatory type of reaction, which may in some instances be harmful and may counteract the beneficial effects of the therapeutic agent. Applying this principle to the present situation, it has been known for a long time that the inert fatty acids have considerable antimycotic properties, yet heretofore these compounds have not been widely used for the treatment of fungus infections of the skin, for the reason, possibly among others, that if these sub-" by which they might produce a local high concentration on the skin, they may be somewhat irritating thereto. If water soluble salts of these fatty acids are used, they may in some cases, be irritating because of the production of an alkaline reaction: while if the free fatty acids are used, they may in some cases, cause irritation because of an undesired increase in the hydrogen ion concentration: and finally, high concentrations of both soluble acids and salts may be irritating because of the surface-active characteristics of the compound itseli'.

While water insoluble agents are as a rule quite inactive or inert in aqueous media, I have discovered that the zinc salts of olefinic acids containing from S to 12 carbon atoms are active antimycotics, when tested by the usual methods on Sabourauds agar and are also highly efl'ective and not irritating when used therapeutically. As an instance of special utility and preference,

it may be noted that undecylenic acid has been clinically demonstrated to be superior to other fatty acids as a therapeutic agent for the treatment of dermatomycosis. Zinc salts of oleflnic 50 acids (such as undecylenic acid) have a tendency to form colloidal solutions and can be obtained in highly divided form. Thus they can be spread evenly on the skin. They have lubricating properties and adhere to the skin, which is highly 55 desirable in producing uniform and sustained therapeutic action. Because of these properties, the zinc salts of olefinic acids are useful components of ointments or powders intended for the application to body surfaces and are one of 60 the essential ingredients of the compositions in accordance with the present invention. oozing body surfaces are benefited by the'applicatlon of finely divided material which absorbs moisture. While there are other finely divided soft powders usedand usable for this purpose, including the zinc salts of paraflinic acids, the zinc salts of oleflnic acids in addition to their useful function as above setforth are quite satisfactory in this respect. The use thereof as an ingredient of a composition of the type herein set forth for the various reasons above set forth is a primary feature of the present invention.

The chemical and chemotherapeutic properties of olefinic acids are per se known, as is also the comparison of these properties with those of corresponding paramnic acids. The differences of these properties may possibly tend to explain to some extent at least, the desirable therapeutic properties of the zinc salts of the oleflnic acids. In particular I have found that they are so inert that they can be applied to the most sensitive parts of the human skin without causing any substantial irritation. This'is especially the case if care is taken that substantially neutral salts of oleflnic acids are used. The dryin properties of these salts are also quite remarkable, which is a desirable characteristic in treating infections of this type. Basic zinc salts of oleflnic acids may also be prepared under properly selected conditions and are quite useful in certain embodiments of the invention.

The composition of the present invention may be briefly summarized as including: a zinc salt of an olefinic acid having 6 to 12 carbon atoms; a carrier which in most instances may be pharmacologically essentially inert and which is suitable for the preparation of the compound in its desired form for topical application, for example suitable respectively for compositions in powder and ointment forms; and optionally added materials-which may be totally omitted or varied as hereinafter set forth, including any. material necessary for controlling the pH of the composition, e. g. in instances when it is made up in the form of an ointment or paste or other non-solid form. These various components and their particular requirements, limitations, scope and proportions will be hereinafter set forth.

I have found that for the reasons above set forth, one essential ingredient of the composir salt may be straight or branched chain. The straight chain acids have been discussed above. As examples of branched chain acids, I have studied the results obtained from the use of the following (all alpha beta unsaturated): alpha, beta-4-ethylhexenoic acid dado mm no mo 11-0 0 0 n alpha, beta-4 ethyloctenoic acid cm-wmacaomon-ooon and alpha, beta pentenoic acid having a cyclohexyl group in the chain CsH11'[CH2]2-CHICH-COOH I have found that branched and straight chain compounds are both effective, although the straight chain compounds are preferred as they are substantially the more active; and that the presence of a saturated hydrocarbon ring group does not negative although it may vary to some extent the fungicidal activity of the compound. The proportions in which this ingredient is to be used will be later more appar ent from further description herein, and is contemplated to be from an effective amount up to 60% or so. In this connection it has been found that when the composition is prepared in powder form, a substantially higher proportion of the zinc salt may sometimes be used than when an ointment is prepared, e. g. an ointment having a moderate content of said zinc salt. In any case in making ointments not over 60% of this material is presently contemplated. Specifically, I now prefer to use zinc undecylenate ZI1[OOC(CH2)BCHZCH2]2 I as a particular and preferred embodiment of the bon atoms. In this connection an acid having 12 carbon atoms, viz. alpha, beta dodecylenic acid (CH:.[CHz]aCH:CHCOOH) has been studied as representing one extreme and acids having 6 carbon atoms, viz. alpha, beta hexenoic acid (CHsECHzhCHZCHCOOH) and omega hexenoic acid (CH2ICH[CH2]3COOH) have been studied as the other extreme. All are about equally useful, although one may be preferred to the other for the treatment of certain conditions or for use in certain carriers; from which I assume that the acids having intermediate numbers of carbon atoms are similarly appropriate and further than the position of the double bond is largely, if not wholly, immaterial. The last is reinforced by the results of tests using acids having 11 carbon atoms (undecylenic acids) wherein in one case the double bond was in the alpha beta position and in another case, in the omega'position. As one example of a zinc salt which I have used in antimycotic compositions, an omega unsaturated undecylenic acid has been employed for making such salt. The acid selected in the making of the invention, although I do not wish to be limited in this respect.

Another ingredient, which I consider essential in the compositions according to my invention, may be defined only as a class of materials and is particularly a carrier of any suitable kind, pref erably a pharmacologically, essentially inert carrier, which may constitute the balance of the proportions, once the other active content or ingredient has been established in the desired proportion.

When the composition of the invention is to be prepared in powder form, I may use such materials as talc, bentonite, diatomaceous earth, or

titania as this inert pulverulent ingredient or carrier.

When the composition is to be prepared for use as a therapeutic in ointment form, I may use any suitable ointment base such as a vanishing cream type of base including a water soluble, high molecular weight substance such as the natural gums, tragacanth or acacia, or synthetic materials such as those known commercially as Carbowax, or methyl cellulose. I also contemplate the use of any desired mixture of natural and artificial or synthetic materials in this respect. I may also use desired amounts, with or in place of these other materials, of such things as petrolatum, lanolin, cetyl alcohol and profound that a preferred form of the invention, which is usable in many instances, has even a closer pH control, preferably between 6 and 7.

There are certain other materials, which may be optionally added to the composition asset forth hereinabove for giving certain desired properties to the composition as a whole. One type of such added materials, which are contemplated in accordance with th present invention, is that known as anionic wetting agents including such materials as sodium tetradecyl sulphate, sodium dioctyl sulfo-succinate and commercial materials known under the trade names of "Aresklene, Areskap, Aresket, Duponol, Nekal," and many others.

Also included in the possible variants of the composition are materials such as hav heretofore been known and/or used in the treatment of infections of this kind, such, for example, as boric acid, salicylic acid, benzoic acid, sulfur (powder) and certain at least of the paraflinic acids, including propionic acid and its salts such as sodium propionate. If desired, the preparation ma include active ingredients as for other purposes, for example, sulfanilamide (in proportion of about of the whole) to control secondary, bacterial infection.

In the ointment form of the invention a certain proportion of water-may, if desired, be included, which may assist in bringing the composition to a desired consistency.

As indicated above, an important feature of the present discovery is that when properly applied to the skin, the finely divided zinc salt of the stated class, such as Zinc undecylenate, constitutes a substance in sparingly solubl form from which an eifective antimycotic agent is slowly liberated, i. e. providing an even or stationary release of an active agent, in quantity sufficient for the desired therapeutic effect and yet without irritating reaction on the skin. For effective realization of such results, in compositions of the character herein claimed, it has been found that the zinc salt should be in the form of a powder of which at least th major part (by weight), and preferably nearly all, is in the range of particle size of not less than 5 microns and not more than 150 microns. A product consisting essentially of the zinc salt in larger granules or crystals may tend to release insufficient amounts of the active antimycotic agent under conditions generall encountered on the skin, 1. e. insufficient amounts for the superior therapeutic effects herein sought to be achieved. Use of the zinc salt in a form of subdivision finer than the range stated above, l. e. wherein the majority of the particles are finer than such range, may tend toward overly rapid release of the antimycotic agent, approaching conditions that occur when the unsaturated fatty acid is present only in a form substantially more dissoluble (in use) than the zinc salt.

For like optimum realization of the slow release of active undecylenate or the like from the zinc salt where the same is embodied in an ointment or lotion, it appears that the carrier should be such as to promote access of moisture to the particles of zinc salt. That is to say, the carrier should either itself contain water in amount equal to at least about 15% of the complete composition (as may b embodied in a suitable emulsion of water-insoluble substances) or should have as its principal base material a watersoluble substance. Examples of substances of the latter class which should then constitute at least the major part of the carrier (excluding water itself), are the various water-soluble substances named above. While in such compositions water itself is a preferred ingredient, it will be understood that the use of a water-soluble carrier in an ointment without inclusion of appreciable water, nevertheless promotes access to the zinc undecylenate by th moisture of the skin, 1. e. as distinguished from a situation where a nonaqueous and insoluble ointment base, if employed (in its semi-fluid state) without water, would tend to seal the particles of zinc undecylenate.

The carrier, moreover, should be such as to provide no departure from the desired pH value (for instances as explained above) which is found to contribute to the described action of the zinc salt; for instance, the carrier should be such that its pH or the pH which it may impart to an aqueous medium with which. it comes into thorough contact, is not less than 4 and not more than 8.

In the case of powders for therapeutic use (including prophylactic use), the zinc salt should be in the particle rangestated above, for like optimum attainment of the peculiarly advantageous results, and the associated carrier should be a finely divided solid of substantially the same particle size as the zinc salt, and very preferably of about the same specific gravity. While waterinsoluble, dry, pulverulent carrier material does not appear to have the same effect in impairment of access to the zinc salt as may occur when a non-soluble, semi-fluid material is used, (without water) for an ointment base, the characteristics of particle size and specific gravity just mentioned are believed of significant importance to avoid de-mixing during storage, handling and use of the prepared antimycotic powder. As will be appreciated, an important function of the carrier is to afford a convenient distribution of the zinc salt over the area of skin to be treated, and achievement of such distribution (for the ultimate action of the zinc salt and its described, slow release of active agent) depends on maintenance of uniform, homogeneous mixture between the zinc salt and the pulverulent carrier. The inert pulverulent ingredients named above, in appropriately fine state of subdivision, appear to satisfy the criterion just stated.

The following data, set forth by way of example, and relating to various proportions of active ingredient and compositions of carrier, will therefore illustrate how the various ingredients may be combined together in accordance with the principles hereinabove set forth and to attain desired results, it being understood that certain compositions may be more desirable in treating certain individual cases than are others.

In powders, the carrier may consist essentially of talc, or of a mixture of zinc stearate and talc (such as 20 parts of the former to 55 parts of the latter) or a mixture of diatomaceous earth and tale (in the proportion of 20 parts of the former to 55 parts of talc) the zinc undecylenate usually representing about 20% of the composition by weight. It will be understood that in the case of powders the ingredients are all preferably prepared in a finely pulverulent form and are mixed together thoroughly until a uniform product is obtained.

To make an ointment, 10. parts by weight of cetyl alcohol, 3 parts each of white petrolatum and lanolin are weighted into a suitable container and melted by heating to 60 C. They are mixed until a uniform product is obtained. In a separate container 10 parts of propylene glycol and 40 parts of water are mixed and heated to 55 to as: 1,osa

60 C. The two mixtures are blended. 0.5 part of sodium tetradecyl sulfate is dissolved in benzol and added to a mixture of 20 parts zinc undecylenate. The benzol is evaporated and the powder dried. The dry powder is added to the molten mixture of other ingredients and stirred. A soft three phase emulsion type of ointment results which has some of the characteristics of a vanishing cream. Sumcient water is theniadded and mixed until a uniform product of 100 parts by weight is obtained.

The above preparation represents a satisfactory form of ointment, but]: further contemplate that the amount of petrolatum-lanolin, cetyl alcohol, propylene glycol and water may be varied within reasonable limits as will be apparent to those skilled in the art and'still yield a product having a desired consistency. Zinc undecylenate may be varied from 10 to 20% or more and the sodium tetradecylsulfate (wetting agent) from 0.1 to 1% without substantially varying the above composition.

In another ointment, the zinc, saltof alpha, beta i-ethylhexenoic acid is used, in an ointment base containing Carbowax 1500" and fCarbow'ax 4000" respectively ,in. amounts of 419%; and 30% of the entire comp'ositio ,the ointment also including propylene glycolin the amount of say 10%, and water to make up the balance of the composition, e. g. 15% "or more. ,Another ointment, otherwise of similar composition, contains zinc undecylenate as the zinc-salt. Another ointment base ingredient, useful-in small quantitles such as a few percent, is Methocel." A further example of a zinc compound suitable for use in compositions of the present invention is zinc nonenoate, which maybe combined in ointments of the character described.

'It will be understood that where it is desirable to adjust the pH of the mixture, particularly in instances of an ointment that may otherwise tend to be on the acid side. a small proportion of a suitable material, such as sodium carbonate, may be included. Instead of substances such as cetyl alcohol, other alcohols may be used such as myristic alcohol; a further ingredient of ointments. e. g. as a substitute for propylene glycol, is glycerol.

To good advantage, in some cases, especially for certain types or localities of fungus infection, other insoluble salts of oiefinic acids of the stated character may be incorporated, such for instance as copper undecylenate. Such compound is relatively insoluble in water, and like zinc undecylenate is only slowly dissoluble in use, e. g. when employed for topical application to the skin.

An example of a lotion, prepared as stable, uniform emulsionsuspending the undecylenate material (zinc undecylenate) in homogeneous dispersion is as follows:

30 parts of sesame oil, 1 part of triethanola- 'mine, 5 parts of the emulsifier Span 80 (e. g. an

emulsifying agent of the sorbitan ester type) and 54 parts of water aremixed and heated to 90 for about half an hour in a steam-dined kettle. The temperature is allowed to cool to 40 C. and parts of zinc undecylenate are-added. The mixture is mixeduntil cooled to room temperature; if desired for maximum uniformity, it is put through a mechanical'homogenizer. The resultins viscous lotion is filled into bottles.

Instead of sesame oil, any one of various other materials such as castor oil, peanutoil, olive oil, or even paraflln or mineral oil can be used. If a thinner emulsion is required, the amount of oil pense of the water (i. e. the water being reduced protanto) The emulsifier used can be any of the emulsifiers usually employed for like purposes, for example, glycerol monostearate, polyethylene glycol monostearate, polyethylene glycol distearate, and non-ionic emulsifiers such as Nyon and Triton, which derive their lyophilic properties from a polyethylene glycol group and their hydrophobic properties from a long chain aliphatic radical or an aromatic hydrocarbon radical or a combination thereof.

In all of the compositions disclosed herein, the carrier material, such as the ointment base or the talc employed in the powder or the emulsified constituents of the lotion, constitutes material which serves (as water or other non-viscous liquid by itself cannot) to disperse or suspend the zinc salt. (such as zinc undecylenate) positively and uniformly throughout the composition. The carrier thus provides a suitable mixture from which the zinc salt does not even partly separate by settling, shaking down, or the like, despite the fact that suchzinc salt is relativelyheavy and cannot, for example, beheld in'suspension in water or like fluid alone. The ointment base or other carrier as employed in the caseof powder or lotion constitutes as dispersing medium making possible the effective topical application of the composition: that is to say, there is thus provided a vehicle which is non-irritating to the skin and which contains the zinc salt of an olefinic acid of the stated character in an even and stable dispersion, providing uniform application and adherence to the skin and permitting attainment of a thorough mixture and reaction of the secretions of the skin with the stated zinc salt.

As fully explained hereinabove, the stated zinc salts are highly effective and non-irritating when used therapeutically, i. e. for treatment of socalled superficial fungus infections. They are of such character as to facilitate their being spread evenly on the skin (especially when embodied in vehicles of the sort stated above), and they have lubricating and like properties highly desirable in producing uniform and sustained therapeutic action. It will now be seen that the compositions set forth herein may be defined as consisting of undecylenate material and other material, such other material comprising a carrier (or vehicle) which has the stated dispersing and uniform suspension characteristics and which is usually present in proportions of at least 40% of the composition. The carrier should also advantageously be such as to cooperate, as explained above, in efl'ectuating the desired slow release of effective antimycotic agents from the active in- I gredient. As an active ingredient the zinc undecylenate or other zinc salt (of the described olefinic acids) is preferably present in amount of say, several percent or more, such zinc salt being properly characterized as only slowly dissoluble in use, relative to compounds such as the olefinic acids per se and their water soluble salts (undecylenic acid, triethanolamine undecylenate and sodium undecylenate) which are substantially more dissoluble in use than the zinc salt. Thus where the undecylenate material consists of zinc undecylenate or of zinc undecylenate with other insoluble compounds such as the copper salt, such undecylenate material may be defined as being all of slowly dissoluble character. That is to say, these compounds especially the zinc undecylenate and like insoluble salts provide an even or stationary release of the active agent, affording uniform and sustained therapeutic action, and infusing or diil'using only slowly in either of the oily or aqueous phases of the skin, so as to avoid a high concentration 01' the active agent locally on the body. Briefly stated, the zinc undecylenate or other zinc compound (of the stated class) constitutes an effective antimycotic agent in sparingly form from which the antimycotic activity is slowly liberated. In the various preferred compositions described, this slow liberation of activity is also controlled (in a manner promoting therapeutic eflectiveness without irritation) by the composition and nature of the carrier.

In some instances the compositions, such as powders, may contain up to 50% or more of zinc undecylenate, it being noted that the range of content 01' the zinc salt in various specific compositions mentioned herein extends up to 60% or such material as active ingredient.

Certain of the above references to extremes in concentrations oi active ingredient or of other ingredients, may not beas desirable for average use as compositions containing such ingredients in intermediate amount, but they have utility and may be desirable in treating certain cases even to a greater extent than the more usually preferred compositions of intermediate proportions.

It is to be understood that the invention is not limited to the specific compositions herein described but may be carried out in other ways without departure from its spirit.

I claim:

1. An antimycotic ointment composition adapted for use as a pharmaceutical and adapted in use to liberate slowly the anion of imdecylenic acid, said composition consisting of: (a) compound material comprising zinc undecylenate as an active ingredient of the composition; and (b) material other than substances containing the anion of an oleflnic acid having from 6 to 12 carbon atoms; all of said compound material being selected from the class consisting of waterinsoluble salts which are only slowly dissoluble in use. and said other material comprising a nonirritating ointment base supporting said zinc undecvlenate in stable, uniform dispersion, said o ntment base being at least 40% of the composition and including water in amount equal to at least 15% of the composition, and said zinc undecylenate being embodied in uniform mixture in the composition.

2. An antimycotic ointment composition adapted for use as a pharmaceutical and adapted in use to liberate slowly the anion of undecylenic acid, said composition consisting of: (a) compound material comprising zinc undecylenate as an active ingredient of the composition: and (b) material other than substances containing the anion of an olefinic acid having from 6 to 12 carbon atoms: all of said compound material being selected from the class consisting of waterinsoluble salts which are only slowly dissoluble in use. and said other material comprising a nonirritating ointment base supporting said zinc undecylenate in stable, uniform dispersion, said ointment ham being at least 40% of the composition and comprising ointment base material of which the major part is water-soluble material with which said zinc undecylenate is embodied in stable, uniform dispersion.

3. An antimycotic powder composition adapted for use as a pharmaceutical and adapted in use to liberate slowly the anion of undccylenic acid, said composition consisting of: (a) compound material comprising zinc undecylenate as an active ingredient of the composition; and (b) material other than substances containing the anion of an olefinic acidhaving from 6 to 12 carbon atoms; all of said compound material being in finely pulverulent form and being selected from the class consisting of water-insoluble salts which are only slowly dissoluble in use, and said other material consisting essentially of a non-irritating,

finel ulverulent, solid carrier, said carrier being,

at least 40% of the composition and consisting of organically inert material intimately mixed with the zinc undecylenate and supporting the latter in stable, uniform dispersion.

4. An antimycotic composition adapted for use as a pharmaceutical, and consisting of a spreadable preparation for topical application composed of finely and uniformly dispersed components and prepared as a free body of matter which can be readily and uniformly spread on the skin to there provide slow liberation of the anion of a mono-olefinic, mono-carboxylic acid having from 6 to 12 carbon atoms, said composition consisting of: (a) compound material comprising as an active ingredient of the composition, the zinc salt of a mono-olefinic mono-carboxylic acid having from 6 to 12 carbon atoms; and (b) material other than substances containing the anion of an olefinic acid having from 6 to 12 carbon atoms; all of said compound material being selected from the class consisting of water-insoluble salts which are only slowly dissoluble in use, and said other material comprising a non-irritating and pharmacologlcally essentially inert carrier mixed intimately and uniformly with said zinc salt and adapted to promote access of said zinc salt to the skin, said carrier being at least 40% of the composition, said zinc salt being embodied in stable, uniform dispersion in the carrier, and said carrier supporting the zinc salt in said stable dispersion, facilitating application of the composition to the skin.

JOHN C. BAKER.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 1,995,663 Bollmann Mar. 26, 1935 2,427,022 Russ et al Sept. 9, 194'? 2,466,663

OTHER REFERENCES Peck: J. Investigative Dermatology, Aug. 1936, pages 237-238, 251, 252.

Hopkins: J. of Investigative Dermatology, vol. 7, 1946, pages 239-253. I

Keeney: J. Clinical Investigations, vol. XXIII, No. 6, pages 921, 929-930. Nov. 1944, Proceeding of the 36th Annual Meeting of the American Society for Clinical Investigation held in Atlantic City, N. J., May 8, 1944.

Harris: J. A. M. A, Feb. 6, 1943, pages 403-405.

Russ et a1 Apr. 5, i949 Certificate of Correction Patent No. 2,511,032 June 13, 1950 JOHN CQBAKER It is hereby certified that error appears in the printed specification of the above numbered patent requn'mg correctlon as follows: Y

Column 1, line 24, for fProponic read Proptonie; column 8, line 32, for the word as read a; column 9, lme 13, after sparingly insert soluble;

and that the said Letters Patent should be read as corrected above, so that the same may conform to the record of the case in the Patent Ofiice.

Signed and sealed this 21st day of November, A. D. 1950.

THOMAS F. MURPHY,

Assistant Commissioner of Patents. 

4. AN ANTIMYCOTIC COMPOSITION ADAPTED FOR USE AS A PHARMACEUTICAL, AND CONSISTING OF A SPREADABLE PREPARATION FOR TOPICAL APPLICATION COMPOSED OF FINELY AND UNIFORMLY DISPERSED COMPONENTS AND PREPARED AS A FREE BODY OF MATTER WHICH CAN BE READILY AND UNIFORMLY SPREAD ON THE SKIN TO THERE PROVIDE SLOW LIBERATION OF THE ANION OF A MONO-OLEFINIC, MONO-CARBOXYLIC ACID HAVING FROM 6 TO 12 CARBON ATOMS, SAID COMPOSITION CONSISTING OF: (A) COMPOUND MATERIAL COMPRISING AS A ACTIVE INGREDIENT OF THE COMPOSITION, THE ZINC SALT OF A MONO-OLEFINIC MONO-CARBOCYLIC ACID HAVING FROM 6 TO 12 CARBON ATOMS; AND (B) MATERIAL OTHER THAN SUBSTANCES CONTAINING THE ANION OF AN OLEFINIC ACID HAVING FROM 6 TO 12 CARBON ATOMS; ALL OF SAID COMPOUND MATERIAL BEING SELECTED FROM THE CLASS CONSISTING OF WATER-INSOLUBLE SALTS WHICH ARE ONLY SLOWLY DISSOLUBLE IN USE, AND SAID OTHER MATERIAL COMPRISING A NON-IRRITATING AND PHARMACOLOGICALLY ESSENTIALLY INERT CARRIER MIXED INTIMATELY AND UNIFORMLY WITH SAID ZINC SALT AND ADAPTED TO PROMOTE ACCESS OF SAID ZINC SALT TO THE SKIN, SAID CARRIER BEING AT LEAST 40% OF THE COMPOSITION, SAID ZINC SALT BEING EMBODIED IN STABLE, UNIFORM DISPERSION IN THE CARRIER, AND SAID CARRIER SUPPORTING THE ZINC SALT IN SAID STABLE DISPERSION, FACILITATING APPLICATION OF THE COMPOSITION TO THE SKIN. 